(ORDO NEWS) — Inspired by how molecules interact in nature, UNSW medical researchers are developing versatile nanoscale machines to expand their functional range.
To withstand the harsh conditions inside living organisms, molecular machines must be robust and operate continuously for long periods of time.
At the same time, they must adapt to different needs and changing environmental conditions by quickly replacing molecular components to change the configuration of mechanisms.
A team led by Professor Lawrence Lee of the Australian EMBL node at UNSW Medicine & Health in Single Molecule Science reports in the journal ACS Nano how they designed and built molecular machines with rapid component replacement and stability.
“We have taken a synthetic biology approach to this problem by building an artificial nanoscopic machine using DNA and protein components.
The ability to exchange subunits increases functionality, as we see in biology,” said Prof Li, a researcher at the UNSW School of Health Sciences and Center of Excellence. ARC in Synthetic Biology.
He and his team created molecular machines by folding strands of DNA into three-dimensional shapes, a technique called DNA origami. They showed that their DNA nanomachines can carry both DNA and protein cargo, and are generally compatible with other biomolecules and nanoparticles.
The cargo binds at several sites to the DNA receptor and can be displaced by new cargo through a competitive binding process when another cargo is present in solution.
An example of one of the natural machines that embodies the paradox of stability and rapid exchange is the cellular machine that creates copies of DNA – the DNA replisome.
The mechanism of competitive exchange used by the replisome to simultaneously achieve these opposite properties was proposed in an earlier publication in Nucleic Acid Research by the group of Professor Antoine van Oyen from the University of Wollongong, who is also a co-author of this study.
Professor Li and his team have brought this theory to life using DNA nanotechnology and protein engineering. This is the first synthetic system that uses the so-called “multi-site competitive exchange” principle, he said.
Other mechanisms have been reported to confer dual properties of strength and rapid exchange, but so far this dichotomy has not been possible with other biomolecules.
“Until now, all molecular machines synthesized using DNA nanotechnology have been powered by exchanging DNA strands, but exchanging DNA alone somewhat limits the possibilities. Our results expand the functional complexity available for DNA nanotechnology,” says Professor Li.
He believes that there is a lot of knowledge in nature that nanotechnology researchers can use. “Fast exchange and high stability seem like two incompatible states, but there are so many nanoscale machines in nature that behave in this way.”
The field of DNA nanotechnology is still in its infancy. While researchers still have many design challenges to realize the full potential of molecular machines, the ability to create machines that can operate autonomously and adapt to changes in the environment by replacing various biomolecules is a big step towards a range of applications, from creating sensitive “smart “materials to targeted delivery of therapeutic drugs to diseased cells and much more.
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